| Summary: | In higher vertebrates, axons within the differentiated central nervous
system (CNS) possess a very limited capacity for repair after injury. The
following experiments were designed to determine the contributions of CNS
myelin to the lack of regeneration observed following transection of the late
embryonic and hatchling chick spinal cord. The developmental onset of
myelination in the chick begins at embryonic day (E) 13 of the 21 day
developmental period. Spinal cord transections after the developmental onset of
myelination result in little or no neuroanatomical repair or functional recovery.
However, intraspinal injection of complement-binding galactocerebroside (GalC)
antibodies or 04 antibodies (which react with sulfatide, seminolipid and an
unidentified antigen on oligodendrocyte progenitors) plus complement between
E9-E12 results in a delay in the onset of myelination until E17 (developmental
myelin-suppression). A subsequent transection of the spinal cord as late as El 5
(i.e. during the normal restrictive period for repair) results in complete
neuroanatomical regeneration and functional recovery. Spinal cord transections
on El5 in a normally-myelinated embryo result in no neuroanatomical
regeneration or functional recovery. These findings indicate that CNS myelin is
inhibitory to the functional regeneration of transected spinal cord in embryonic
chick (Keirstead et al. 1992).
These studies also suggest that myelin suppression might also facilitate
regeneration after adult spinal cord injury. Hatchling chickens are precocial and their brainstem and spinal cord can be considered in all respects adult-like.
Administration of complement-binding GaIC antibodies or 04 antibodies plus
complement to the hatchling spinal cord results in the transient removal of
spinal cord myelin (immunological demyelination). The thoracic cord of
posthatching day (P)2-P10 chickens were completely transected and
immunological demyelination was simultaneously initiated. Fourteen to 28 days
later, retrograde tract tracing, including double-labeling studies, indicated that
approximately 5-15% of the brainstem-spinal projections had regenerated across
the transection site to lumbar levels. Even though voluntary locomotion was not
observed after recovery, focal electrical stimulation of identified brainstem
locomotor regions evoked either stepping movements or ‘fictive’ stepping in
paralysed animals (collaborative studies, see chapter 5). This indicates that the
transient demyelination of injured hatchling (i.e. mature) chick spinal cord
facilitated axonal regeneration resulting in some functional synaptogenesis with
spinal neurons.
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